60750-23-4Relevant articles and documents
A Bifunctional Metal/Acid Catalyst for One-pot Multistep Synthesis of Pharmaceuticals
Corma, Avelino,Lopez-Prado, Maria Victoria,Sabater, María J.
, p. 499 - 507 (2020/05/25)
Abstract: One inhibitor of the fatty acid transporter FATP4 was synthesized in a three steps one-pot process in the presence of a bifunctional metal/acid catalyst. This molecule which has potential interest for the treatment of the obesity in orlistat (Xenical TM) analogue-based therapies has a 3,4-dihydropyrimidin-2(1H)-one (DHPM) scaffold and was obtained by means of a three one-pot process through successive oxidation, cyclocondensation and transesterification reactions. The one-pot strategy was extended to the synthesis of a series of related ester DHPM derivatives.
Synthesis, biological evaluation and molecular docking study of dihydropyrimidine derivatives as potential anticancer agents
Ghavimi, Reza,Razzaghi-Asl, Nima,Safari, Sahand,Sepehri, Saghi
, (2020/02/04)
A series of dihydropyrimidine analogues were prepared via one-pot Biginelli three-component condensation reaction and characterized by NMR, FT-IR, MS spectra, and element analysis. Subsequently, they were screened for in vitro anticancer effect. These analogues revealed good cytotoxic activity against three human cancer cell lines including MCF-7, HepG-2, and A549. Among these analogues, compounds 4d and 4h were the most potent against three cell lines. Cell viability assays indicated 4a and 4c had lower cytotoxicity. In vitro cytotoxicity study on all synthesized compounds demonstrated that introduction of electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine contributed to the antiproliferative potency. Moreover, in silico molecular docking results stipulated a sign of good correlation between experimental activity and calculated binding affinity. It proved 4d and 4h as the strongest compounds. Binding modes of analogues proposed the involvement of hydrophobic interactions and hydrogen bonds with Eg5 active site. Structure activity relationship studies indicated that incorporating electron withdrawing substituents on C4 position of phenyl ring of dihydropyrimidine are important for this biological activity.
Design, Synthesis, and Anti-HIV-1 Evaluation of a Novel Series of 1,2,3,4-Tetrahydropyrimidine-5-Carboxylic Acid Derivatives
Sepehri, Saghi,Soleymani, Sepehr,Zabihollahi, Rezvan,Aghasadeghi, Mohammad R.,Sadat, Mehdi,Saghaie, Lotfollah,Memarian, Hamid R.,Fassihi, Afshin
, (2018/04/10)
A series of tetrahydropyrimidine derivatives (2a – 2l) were designed, synthesized, and screened for anti-HIV-1 properties based on the structures of HIV-1 gp41 binding site inhibitors, NB-2 and NB-64. A computational study was performed to predict the pharmacodynamics, pharmacokinetics, and drug-likeness features of the studied molecules. Docking studies revealed that the carboxylic acid group in the molecules forms salt bridges with either Lys574 or Arg579. Physiochemical properties (e.g., molecular weight, number of hydrogen bond donors, number of hydrogen bond acceptors, and number of rotatable bonds) of the synthesized compounds confirmed and exhibited that these compounds were within the range set by Lipinski's rule of five. Compounds 2e and 2k with 4-chlorophenyl substituent and 4-methylphenyl group at C(4) position of the tetrahydropyrimidine ring was the most potent one among the tested compounds. This suggests that these compounds may serve as leads for development of novel small-molecule HIV-1 inhibitors.
